Whole Brain Radiation Therapy With Boost to Metastatic Tumor Volume Using RapidArc

Neoplasm Metastasis Clinical Trial

Official title:

Whole Brain Radiation Therapy With Simultaneous Boost to Gross Metastatic Tumor Volume Using Volumetric Modulated Arc Therapy (RapidArc)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01218542
• Other study ID #: IRB00045035
• Secondary ID: WCI1784-10
• Status: Completed
• Phase: N/A
• Start date: September 22, 2010
• Est. completion date: June 3, 2020

Study information

• Verified date: June 2021
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Brain metastases are the most common adult intracranial tumor, occurring in approximately 10% to 30% of adult cancer patients, and represent an important cause of morbidity and mortality. The most widely used treatment for patients with multiple brain metastases is whole brain radiation therapy (WBRT). The use of WBRT after resection or stereotactic radiosurgery (SRS) has been proven to be effective in terms of improving local control of brain metastases.

RapidArc (RA) (Varian Medical Systems, Palo Alto, CA) is a new method of delivering radiation that uses "arcs" to deliver highly conformal intensity modulated three dimensional dose distributions. The purpose of this investigation is to evaluate an alternative strategy for giving WBRT with highly focal boost to gross visible lesions in patients with brain metastasis.

Given the limitations of the SRS boost technique, the purpose of our investigation is to evaluate an alternative strategy for giving WBRT with highly focal boost to gross visible lesions in patients with brain metastasis. In this study, we plan to assess the tolerability of using volumetric modulated arc therapy (RapidArc) on patients with brain metastasis to simultaneously treat the entire brain with a concomitant focal boost to grossly identified lesions on MRI scan to try to improve local control and reduce neurocognitive toxicities.

This previous version of this study was a phase I dose escalation trial giving 25 Gy in 10 fractions to the whole brain with simultaneous infield boost (SIB) to a total of 45 Gy in 10 fractions to gross brain metastatic disease. Prior to this, patients were enrolled onto one of two cohorts with whole brain dose of 30 Gy in 10 fractions with SIB to total of 45 Gy in 10 fractions to gross brain metastatic disease or whole brain dose of 37.5 Gy in 15 fractions with SIB to total of 52.5 Gy in 15 fractions to gross brain metastatic disease. A total of 12 patients have been previously enrolled on this trial. No patients have experienced a dose limiting toxicity (grade 3 or above) at least possibly due to study therapy. Also, no patients experienced local brain failure/progression at a site of treated metastatic brain disease. Based on this, we no longer feel that dose escalation to the gross brain disease is warranted and would proceed with a single arm pilot study treating patients with 25 Gy in 10 fractions to the whole brain with simultaneous infield boost (SIB) to a total of 45 Gy in 10 fractions to gross brain metastatic disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: June 3, 2020
• Est. primary completion date: June 3, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pathologic proven diagnosis of solid tumor malignancy.

• Age = 18.

• KPS = 70.

• Mini Mental Status Exam (MMSE) = 18 prior to study entry.

• RPA class I (KPS = 70, primary cancer controlled, age < 65, metastases in brain only) or class II (lack of one or more of class I criteria).

• One to ten brain metastatic lesions.

Exclusion Criteria:

• Previous whole brain radiation therapy.

• Previous radiosurgery to any currently progressive gross metastatic disease.

• Previous radiosurgery to any intracranial site within the prior 6 weeks.

• Recursive partitioning analysis (RPA) class III (KPS < 70).

• Radiosensitive (eg. small cell lung carcinomas, germ cell tumors, leukemias, or lymphomas) or unknown tumor histologies.

• Concurrent chemotherapy (no chemotherapy starting 14 days before start of radiation).

• Evidence of leptomeningeal disease by MRI and/or cerebrospinal fluid (CSF) cytology.

• Current pregnancy.

• No metastases to brain stem, midbrain, pons, or medulla or within 7 mm of the optic apparatus (optic nerves and chiasm).

Related Conditions & MeSH terms

• Neoplasm Metastasis

Intervention

Radiation:
• Volumetric modulated arc therapy
Using volumetric modulated arc therapy to give simultaneous infield boost to gross metastatic brain lesions during whole brain radiation therapy.

Locations

Country	Name	City	State
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University/Winship Cancer Institute	Atlanta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Emory University

Country where clinical trial is conducted

United States, 

References & Publications (10)

Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, Werner-Wasik M, Demas W, Ryu J, Bahary JP, Souhami L, Rotman M, Mehta MP, Curran WJ Jr. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet. 2004 May 22;363(9422):1665-72. — View Citation

Arbit E, Wronski M, Burt M, Galicich JH. The treatment of patients with recurrent brain metastases. A retrospective analysis of 109 patients with nonsmall cell lung cancer. Cancer. 1995 Sep 1;76(5):765-73. — View Citation

Bauman G, Yartsev S, Fisher B, Kron T, Laperriere N, Heydarian M, VanDyk J. Simultaneous infield boost with helical tomotherapy for patients with 1 to 3 brain metastases. Am J Clin Oncol. 2007 Feb;30(1):38-44. — View Citation

CHAO JH, PHILLIPS R, NICKSON JJ. Roentgen-ray therapy of cerebral metastases. Cancer. 1954 Jul;7(4):682-9. — View Citation

Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T, McKenna WG, Byhardt R. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys. 1997 Mar 1;37(4):745-51. — View Citation

Lagerwaard FJ, van der Hoorn EA, Verbakel WF, Haasbeek CJ, Slotman BJ, Senan S. Whole-brain radiotherapy with simultaneous integrated boost to multiple brain metastases using volumetric modulated arc therapy. Int J Radiat Oncol Biol Phys. 2009 Sep 1;75(1):253-9. doi: 10.1016/j.ijrobp.2009.03.029. Epub 2009 Jul 4. — View Citation

Patchell RA, Regine WF. The rationale for adjuvant whole brain radiation therapy with radiosurgery in the treatment of single brain metastases. Technol Cancer Res Treat. 2003 Apr;2(2):111-5. Review. — View Citation

Sundström JT, Minn H, Lertola KK, Nordman E. Prognosis of patients treated for intracranial metastases with whole-brain irradiation. Ann Med. 1998 Jun;30(3):296-9. — View Citation

Zhong J, Waldman AD, Kandula S, Eaton BR, Prabhu RS, Huff SB, Shu HG. Outcomes of whole-brain radiation with simultaneous in-field boost (SIB) for the treatment of brain metastases. J Neurooncol. 2020 Mar;147(1):117-123. doi: 10.1007/s11060-020-03405-y. E — View Citation

Zimm S, Wampler GL, Stablein D, Hazra T, Young HF. Intracerebral metastases in solid-tumor patients: natural history and results of treatment. Cancer. 1981 Jul 15;48(2):384-94. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of Participants With Locoregional Control of Treating Brain Metastasis Patients	The cumulative incidences of recurrence locally and in the whole brain were reported at the patient level.	Locoregional control at 1 year
Secondary	Brain Progression-free Survival	Defined as period of time from study entry to to death from any cause or brain tumor recurrence or progression.	11 months median follow up period.
Secondary	Overall Survival	Defined time from study entry to death from any cause.	11 months median follow up period.
Secondary	Neurocognitive Effects	Neurological test score were assessed using the Hopkins Verbal Learning Test-Revised (HVLT).; In the HVLT 12 words are read and the participant is asked to recall them, this is completed 3 times.; Total words recalled are summed to give a score for Total Recall (0-36, higher scores demonstrated better recall).; Delayed recall is conducted 20-25 minutes later on the same list of 12 words (scored 0-12 with higher scores demonstrating better recall).; Retention is calculated as the percent of words recalled (scored 0-100, higher scores representing better recall).; Recognition Discrimination is tested by a series of yes/no responses from the participant identifying 12 target words from a list of 24 and calculated by the number of true positives minus the number of true negatives with higher scores indicating a better outcome.	11 months median follow up period.
Secondary	Quality of Life as Measured by the FACT-Br Subscales	The Functional Assessment of Cancer Therapy-Brain (FACT-Br) were summed to create the FACT brain trial outcome index (FACT-BR TOI), FACT general (FACT-G), and FACT brain total (FACT-BR Total).; Three FACT scales were calculated. The higher the value the better the score, i.e., the better the quality of life perceived by patient.; FACT BR TOTAL (FACT-G + BrCS, possible range 0 - 200) FACT-BR TOI (Trial Outcome Index = Physical Well Being _ Functional Well Being +BrCS, possible range 0 - 148) FACT-G (Fact General, possible range 0 - 108)	11 month median follow up